Glomerular arteriolar vasoconstriction and tubulointerstitial injury are observed before glomerular damage occurs in models of hypertension. High interstitial ATP concentrations, caused by the increase in arterial pressure, alter renal mechanisms involved in the long-term control of blood pressure, autoregulation of glomerular filtration rate and blood flow, tubuloglomerular feedback (TGF) responses, and sodium excretion. Elevated ATP concentrations and augmented expression of P2X receptors have been demonstrated under a genetic background or induction of hypertension with vasoconstrictor peptides. In addition to the alterations of the microcirculation in the hypertensive kidney, the vascular actions of elevated intrarenal angiotensin II levels may be mitigated by the administration of broad purinergic P2 antagonists or specific P2Y12, P2X1, and P2X7 receptor antagonists. Furthermore, the prevention of tubulointerstitial infiltration with immunosuppressor compounds reduces the development of salt-sensitive hypertension, indicating that tubulointerstitial inflammation is essential for the development and maintenance of hypertension. Inflammatory cells also express abundant purinergic receptors, and their activation by ATP induces cytokine and growth factor release that in turn contributes to augment tubulointerstitial inflammation. Collectively, the evidence suggests a pathophysiological activation of purinergic P2 receptors in angiotensin-dependent hypertension. Coexistent increases in intrarenal angiotensin II and activates Ang II AT1 receptors, which interacts with over-activated purinergic receptors in a complex manner, suggesting convergence of their post-receptor signaling processes.

中文翻译：

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嘌呤能和血管紧张素 II 受体功能在血管紧张素 II 依赖性高血压肾血管反应和肾损伤中的整合。


在高血压模型中，在肾小球损伤发生之前观察到肾小球小动脉血管收缩和肾小管间质损伤。动脉压升高引起的高间质 ATP 浓度会改变涉及血压长期控制、肾小球滤过率和血流量自动调节、肾小球反馈 (TGF) 反应和钠排泄的肾脏机制。在遗传背景或血管收缩肽诱导高血压的情况下，ATP 浓度升高和 P2X 受体表达增强已得到证实。除了高血压肾脏微循环的改变之外，通过施用广泛的嘌呤能 P2 拮抗剂或特异性 P2Y12、P2X1 和 P2X7 受体拮抗剂也可以减轻肾内血管紧张素 II 水平升高的血管作用。此外，用免疫抑制剂化合物预防肾小管间质浸润可减少盐敏感性高血压的发生，表明肾小管间质炎症对于高血压的发生和维持至关重要。炎症细胞还表达丰富的嘌呤能受体，它们被 ATP 激活会诱导细胞因子和生长因子释放，进而加剧肾小管间质炎症。总的来说，证据表明血管紧张素依赖性高血压中嘌呤能 P2 受体的病理生理学激活。肾内血管紧张素 II 共存增加并激活 Ang II AT1 受体，后者以复杂的方式与过度激活的嘌呤能受体相互作用，表明其受体后信号传导过程的收敛。